PROGRAM (provided by applicant): The unifying theme of the Program Project is the challenge of transferring genes to progenitor and differentiated cells relevant to disorders of the heart, lung, and blood. For this competing renewal, the focus has been further concentrated on gene transfer relevant to blood vessels, particularly endothelial cells. Over the past several years, the Principal Investigators have developed a number of collaborative relationships centered on the use of the Weill Cornell Belfer Gene Therapy Core Facility (BGTCF), that provides 12,000 ft-2 of state-of-the-art laboratory space with the expertise and infrastructure for the design, creation, production, and assessment of gene transfer vectors. Under the direction of R. Crystal, Program Project Director, the proposal includes four projects and four cores, including: Project 6, S. Raffi, PI -regulation of hemangiogenesis by adenoviral E4 genes; Project 7, B. Hempstead, PI - role of the neurotrophins in angiogenesis; Project 8, P. Leopold, PI - trafficking of adenovirus vectors in endothelial cells; and Project 9, R. Crystal, PI - manipulation of VEGF splicing in angiogenic gene therapy; Core 9001-vector; Core 9003-cell biology; Core 9005-analysis; Core9006-experimental animals. By creating an interactive, interdependent environment of Pis and co-PIs with a history of extensive collaborations, and long experience in the biology of progenitor and/or differentiated cells relevant to the vascular system and gene transfer vectors relevant to these cell target, and capitalizing on the extensive gene transfer-relevant core infrastructure at Weill Cornell, a competing renewal has been crafted that far exceeds the scope of what a single investigator or laboratory could focus on this subject.